Chronic stress plasticity in the hypothalamic paraventricular nucleus.

Proper integration and execution of the physiological stress response is essential for maintaining homoeostasis. Stress responses are controlled in large part by the paraventricular nucleus (PVN) of the hypothalamus, which contains three functionally distinct neural populations that modulate multiple stress effectors: (1) hypophysiotrophic PVN neurons that directly control the activity of the hypothalamic-pituitary-adrenocortical (HPA) axis; (2) magnocellular neurons and their secreted neurohypophysial peptides; and (3) brainstem and spinal cord projecting neurons that regulate autonomic function. Evidence for activation of PVN neurons during acute stress exposure demonstrates extensive involvement of all three effector systems. In addition, all PVN regions appear to participate in chronic stress responses. Within the hypophysiotrophic neurons, chronic stress leads to enhanced expression of secreted products, reduced expression of glucocorticoid receptor and GABA receptor subunits and enhanced glutamate receptor expression. In addition, there is evidence for chronic stress-induced morphological plasticity in these neurons, with chronic drive causing changes in cell size and altered GABAergic and glutamatergic innervation. The response of the magnocellular system varies with different chronic exposure paradigms, with changes in neurohypophysial peptide gene expression, peptide secretion and morphology seen primarily after intense stress exposure. The preautonomic cell groups are less well studied, but are likely to be associated with chronic stress-induced changes in cardiovascular function. Overall, the PVN is uniquely situated to coordinate responses of multiple stress effector systems in the face of prolonged stimulation, and likely plays a role in both adaptation and pathology associated with chronic stress.